Statins, anyone? Options

[gigem99]

Although my cholesterol levels are extremely good (LDL - 84, HDL- 89, a few months ago; my PCP is jealous), my heart doc wants me to start taking a statin (Lipitor). Now, she's a very bright, Harvard-educated (and cute) young lady, but I'm leery of starting another medication. I think sometimes the medical establishment takes a "go-with-the-crowd" mentality - and I don't get it. I remember 30-35 years ago when every doc around cried "DON'T EAT EGGS - too high in cholesterol!!!"

I have just about no hair left on my lower legs - admittedly symptomatic of peripheral vascular disease, so I think her thinking is that she wants to head off trouble at the pass. However, my thinking is that statins are very powerful drugs with some fairly serious side effects. I'm inclined to refuse her suggestion.

Does anyone have any experiences (good/bad/indifferent) with this class of drug?

Tom

[Beowulf]

I don't have any experience with that specific drug, but my endo has me on Zocor, well, the generic one anyway. He told me that diabetics have a higher risk of heart attack due to cholesterol levels than non-D people. So he always suggests to his patients that they start on it. I think he said that of the 100 or so patients that he deals with only one or two aren't taking it. I haven't had any side effects, other than lower cholesterol levels (yay!) I've been taking in for a little more than a year. So far so good!

Justin

[Arlene S.]

Although my cholesterol levels are extremely good (LDL - 84, HDL- 89, a few months ago; my PCP is jealous), my heart doc wants me to start taking a statin (Lipitor). Now, she's a very bright, Harvard-educated (and cute) young lady, but I'm leery of starting another medication. I think sometimes the medical establishment takes a "go-with-the-crowd" mentality - and I don't get it. I remember 30-35 years ago when every doc around cried "DON'T EAT EGGS - too high in cholesterol!!!"

I have just about no hair left on my lower legs - admittedly symptomatic of peripheral vascular disease, so I think her thinking is that she wants to head off trouble at the pass. However, my thinking is that statins are very powerful drugs with some fairly serious side effects. I'm inclined to refuse her suggestion.

Does anyone have any experiences (good/bad/indifferent) with this class of drug?

Tom

My HDL has always been high and my Trigs low (38-54) but my LDL was over 100 so my doctor put me on Lipitor several years ago and it has worked. I also read that statins can prevent stroke. A friend who is not a diabetic recently had a stroke and he is in pretty bad shape. If she wants to put you on a low dose it's probably not a bad idea. But that's just my opinion. I see a cardiologist only because I am a diabetic.

[gritsgalky]

Hey Arlene,

I do have high cholestrol and I take Lipitor but it is my undertanding that the statins is also good for the kidneys. It keeps the valve that releases urine into the kidney from leaking the urine back. kinda like a reflux situation. I have been on Lipitor for several years and have not had any issues with it except now my cholestrol is normal. I don't want to take on any new/more medications if not indicated and it is always good to question and be an informed consumer. But I take the statin for the kidney as well as a blood pressure medication. Better living through chemistry.

the bionic.
gritsgalky

[Cin]

My endo has me on Simvastatin for my cholesterol, no side effects except for better total cholesterol readings. I'm wondering though if it would be safe to take fish oil capsules with the Simvastatin. Anyone know?

This post has been edited by Cin: Mar 25 2009, 01:16 AM

[Linda B]

I have been on Lipitor 10 mg for at least 5 or 6 years. I can't remember when I went on it. I have had no side effects. Like Arlene, my HDL is high, my triglycerides were low, but my LDL was too high. The 10 mg Lipitor works great, so much so that my numbers are all excellent. I have heard that many endos put all their diabetics on statins.

I also take Fish Oil in addition to the Lipitor. My PCP had no problem when I asked if he thought Fish Oil was a good idea, he said yes. I was told by a nutritionist that the Lipitor can prevent plaque from building up but does nothing for any that is already there. Fish Oil is supposed to break up existing plaque. I had an ultrasound and I have very minor buildup in my Abdominal Aorta, so I decided to take the Fish Oil.

I just visited a cousin who is also on a statin and her pcp prescribes Fish Oil.

Linda B.

[Arlene S.]

Hey Arlene,

I do have high cholestrol and I take Lipitor but it is my undertanding that the statins is also good for the kidneys. It keeps the valve that releases urine into the kidney from leaking the urine back. kinda like a reflux situation. I have been on Lipitor for several years and have not had any issues with it except now my cholestrol is normal. I don't want to take on any new/more medications if not indicated and it is always good to question and be an informed consumer. But I take the statin for the kidney as well as a blood pressure medication. Better living through chemistry.

the bionic.
gritsgalky

Hi Gritsgalky,

Lipitor (10 mg daily) has brought my LDL down considerably and I haven't had any problems with the drug. In fact, it is one of the few drugs I take that doesn't have a generic but I'm afraid to switch. As far as kidneys I take quiipril (Accupril), an ACE inhibitor that's supposed to protect the kidneys in addition to lowering the blood pressure. I didn't consent to either of the drugs until I did some research but the fact that these drugs have been known to help prevent stroke, heart attack and kidney failure is reason enough to take them. Of course there is no guarantee but we try.

[Cin]

I have been on Lipitor 10 mg for at least 5 or 6 years. I can't remember when I went on it. I have had no side effects. Like Arlene, my HDL is high, my triglycerides were low, but my LDL was too high. The 10 mg Lipitor works great, so much so that my numbers are all excellent. I have heard that many endos put all their diabetics on statins.

I also take Fish Oil in addition to the Lipitor. My PCP had no problem when I asked if he thought Fish Oil was a good idea, he said yes. I was told by a nutritionist that the Lipitor can prevent plaque from building up but does nothing for any that is already there. Fish Oil is supposed to break up existing plaque. I had an ultrasound and I have very minor buildup in my Abdominal Aorta, so I decided to take the Fish Oil.

I just visited a cousin who is also on a statin and her pcp prescribes Fish Oil.

Linda B.

Thanks Linda. I appreciate your reply. As of now, I am taking:
Simvastatin 10mg
Levothyroxine 150mcg
Multi Vitamin
so, I'm guessing that the fish oil won't hurt any. I've been on Simvastain approximately 9 months now and my total cholesterol has dropped from 208 to 180. Not perfect but at least it's going down.

[farside]

Statins have many side effects. Two are listed below.


Muscles and Statins

A University of Alabama at Birmingham physiology professor, Dr. Thalacker-Mercer, has found that simvastatin (Zocor) inhibit muscle repair and regeneration. The title of her work is ““Simvastatin Reduces Human Primary Satellite Cell Proliferation in Culture” and was publish at the September 2008 meeting of the American Physiological Society.

A synopsis of her work can be found here http://www.the-aps.org/press/journal/08/32.htm

The Brain and Statins

In addition, Yeon-Kyun Shin, a biophysics professor at Iowa State University, has found that statins that inhibit the liver from making cholesterol may also keep the brain from making cholesterol, which is vital to efficient brain function.

Professor Shin said, "If you try to lower the cholesterol by taking medicine that is attacking the machinery of cholesterol synthesis in the liver, that medicine goes to the brain too. And then it reduces the synthesis of cholesterol which is necessary in the brain,"

Source -- http://www.public.iastate.edu/~nscentral/n.../feb/shin.shtml

Kind Regards,
Farside

[JohnG]

Although my cholesterol levels are extremely good (LDL - 84, HDL- 89, a few months ago; my PCP is jealous), my heart doc wants me to start taking a statin (Lipitor). Now, she's a very bright, Harvard-educated (and cute) young lady, but I'm leery of starting another medication. I think sometimes the medical establishment takes a "go-with-the-crowd" mentality - and I don't get it. I remember 30-35 years ago when every doc around cried "DON'T EAT EGGS - too high in cholesterol!!!"

I have just about no hair left on my lower legs - admittedly symptomatic of peripheral vascular disease, so I think her thinking is that she wants to head off trouble at the pass. However, my thinking is that statins are very powerful drugs with some fairly serious side effects. I'm inclined to refuse her suggestion.

Does anyone have any experiences (good/bad/indifferent) with this class of drug?

Tom

Hi Tom
I have good cholesterol numbers but still see a Cardiologist every year I have been taking a mild low dose beta blocker for 10 years
and it's just a prophylactic to slow down related diabetes damage. Last year they tried to get me to take Lipitor and I asked them why
they would prescribe it to some one with no problems and they told me they like to stay with a proven treatment plan across the board
for all there patents. I challenged this and they set out to prove they could find something wrong with me. After Two nuclear stress tests
and scanning of my heart and legs they said everything looked good and there was probably no reason to take the Lipitor. They
said most people 55 years old have some signs of heart disease and there insurance will balk at running a good set of tests if they
have not had a major event .The testing was about 9,500.00 dollars but my insurance company (UHC) will pay for all of this testing if your a Diabetic.
What started all of this was a simple office visit before Cycling season, just needed to know how hard I could push it.

My Diabetes has caused me to have fatty liver disease in the past so I never take anything that would cause liver damage.
It's in my best interest to control problems with exercise and a healthy diet.

Note:
My mother is 84 years old and in perfect physical condition she goes to the gym three times a week has a personal
trainer works in the yard and cuts her grass. With all of this she still has high cholesterol and without medication
she would probably not be in good shape today.

JohnG

[Dave_]

Although my cholesterol levels are extremely good (LDL - 84, HDL- 89, a few months ago; my PCP is jealous), my heart doc wants me to start taking a statin (Lipitor). Now, she's a very bright, Harvard-educated (and cute) young lady, but I'm leery of starting another medication. I think sometimes the medical establishment takes a "go-with-the-crowd" mentality - and I don't get it. I remember 30-35 years ago when every doc around cried "DON'T EAT EGGS - too high in cholesterol!!!"

I have just about no hair left on my lower legs - admittedly symptomatic of peripheral vascular disease, so I think her thinking is that she wants to head off trouble at the pass. However, my thinking is that statins are very powerful drugs with some fairly serious side effects. I'm inclined to refuse her suggestion.

Does anyone have any experiences (good/bad/indifferent) with this class of drug?

Tom

I've had all SORTS of experience with statins--some good, some bad, and it's still to be determined.

FIrst of all, I took Pravachol (pravastatin) for roughly 5 years without incident. Then, suddenly my AST and ALT numbers began climbing alarming, about 13 months ago. I stopped the drug, retook blood tests a month later and the numbers dropped. doc put me on 1/2 dose, took test again within a month of restarting--AST and ALT numbers went higher than before! stopped the meds and over the span of several months the numbers came back down, eventually to under the lab limits.

That wasn't the end of the story. My endo wanted me on a statin regardless, so after some discussion, I agreed to take Simvastatin every other day. My ALT and AST numbers were fine when I started and I was very concerned about what would happen to them upon taking the Simvastatin. To my delight and utter surprise, the blood test I took within 3-1/2 weeks of starting showed my AST and ALT actually dropped! They were 18 and 15 respectively--far below the limits. I will continue to have periodic bloodwork to watch over those numbers. Other than the elevated bloodwork levels, I've not noticed any adverse effect from taking statins and the statin does reduce my cholesterol numbers significantly from the low 200's to the 155-180 range.

This post has been edited by Spike: Mar 25 2009, 04:37 PM

[tedm]

My MD, who is alternative medicine oriented, warned me that statins interfere with the body's production of Co-enzyme Q10 (CoQ10) which is essential for heart health. A quick Google search brings up pages such as this warning about this. He reluctantly put me on a statin for my cholesterol levels, while insisting that I also take a CoQ10 supplement. Fortunately, Zocor (Simvastatin) has been very effective for me at a low dose but I still take my CoQ10.

This danger is basically rejected by mainstream medicine, so take this all with your favorite-sized slat grain. However, I'd suggest that a CoQ10 supplement is a small cost for some insurance, especially given that CoQ10 is acknowledged as being required for heart health and, as diabetics, we need to take extra care of our hearts.

[karen]

My experience with statins was horrible. I took the drug for less than two weeks and the muscle aches and constant pain was severe. These aches and pains started quickly for me. I was unable to function much less do any kind of exercise. It hurt to hold my head up! I stopped taking the statin and suffered for a couple of months with the aches. I wouldn't take them and certainly not with 'normal' numbers.

[gigem99]

Yesterday, I went to see my endo and specifically asked him about starting Lipitor (or any statin, for that matter). He said the studies that showed the benefits of statins for diabetics were almost all for type 2's. He said I'm a little different. I explained my reluctance to just start taking a pill for taking a pill's sake - prophylactic effect.

He recommended that I have a relatively new blood test called h.s. CRP - high sensitivity c-reactive protein. He said if it came in low (<1), I probably didn't need the statin. If it was mid-range (1-3) it was pretty much a judgement call. If over 3, he would also recommend the statin.

I'll have the blood drawn in a couple of weeks before I go back to see the young heart doc. The jury's still out on her. I haven't decided whether to trust her like I do my endo.

I do want to thank everyone for their replies - y'all have really helped me a lot in making up my mind. I've had so many docs I didn't like/respect that I have to make up my mind what's best for me.

Tom

[Liz]

I was on Lipitor for about a year, mid-2005 through mid-2006. My CDE put me on Lipitor 10mg and fosinopril because at the time my cholesterol was elevated as well as blood pressure, although neither was horrible. A year after starting the pump I was able to lose a lot of weight and my numbers came back down. My CDE told me to stop taking both medications and I did. Last Fall she said I might end up back on Lipitor because my numbers were creeping up. I saw her last month and my numbers were (barely) in range so she's just going to watch and see what happens. My total cholesterol was 178, LDL 98, HDL 75 and triglycerides 25.

I keep reading the pros & cons of taking statins & ACE inhibitors as a prevention. I had no side effects from the medications but I just hate taking medications and decided I'd rather not go back on them unless there's a real need.

[gigem99]

I keep reading the pros & cons of taking statins & ACE inhibitors as a prevention. I had no side effects from the medications but I just hate taking medications and decided I'd rather not go back on them unless there's a real need.

I did have to start taking an ACE inhibitor, because my blood pressure was consistently running about 160/80. I don't have a problem doing that - although now I've added a diuretic and a calcium channel blocker. Like you, Liz, I'd prefer not to take the med's unless "there's a real need". For the hypertension, there is a real need. For the cholesterol, there's not.

BTW - it's good to see you back.

Tom

[Liz]

I did have to start taking an ACE inhibitor, because my blood pressure was consistently running about 160/80. I don't have a problem doing that - although now I've added a diuretic and a calcium channel blocker. Like you, Liz, I'd prefer not to take the med's unless "there's a real need". For the hypertension, there is a real need. For the cholesterol, there's not.

BTW - it's good to see you back.

Tom

Although I can't remember what my BP was 4 years ago, I was surprised when I was told it was high. I never, ever had issues with BP and would often read a little low. I've had no problems since stopping the fosinopril 3 years ago. My boss has a BP monitor in his office and I should probably borrow it every so often to keep an eye on it, just in case. I would not fight taking a pill if my numbers call for it but it would annoy me to take it "just in case".

[Mariya Blas]

Yesterday, I went to see my endo and specifically asked him about starting Lipitor (or any statin, for that matter). He said the studies that showed the benefits of statins for diabetics were almost all for type 2's. He said I'm a little different. I explained my reluctance to just start taking a pill for taking a pill's sake - prophylactic effect.

He recommended that I have a relatively new blood test called h.s. CRP - high sensitivity c-reactive protein. He said if it came in low (<1), I probably didn't need the statin. If it was mid-range (1-3) it was pretty much a judgement call. If over 3, he would also recommend the statin.

I'll have the blood drawn in a couple of weeks before I go back to see the young heart doc. The jury's still out on her. I haven't decided whether to trust her like I do my endo.

I do want to thank everyone for their replies - y'all have really helped me a lot in making up my mind. I've had so many docs I didn't like/respect that I have to make up my mind what's best for me.

Tom

HMG-CoA Reductase Inhibitors (Statins)

HMG-CoA reductase inhibitors, also known as statins, are the most effective drugs for lowering LDL cholesterol levels, and they cause few adverse effects. As a result, statins are the most widely used cholesterol-lowering agents. At this time, six statins are available: atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin. In 2004, two of these drugs—atorvastatin [Lipitor] and simvastatin [Zocor]—were ranked first and second among the best-selling drugs in the United States, generating $16 billion in sales.

Beneficial Actions

The statins have multiple actions that can benefit patients with atherosclerosis. The most obvious is reduction of LDL cholesterol. However, other actions are also involved.

Reduction of LDL Cholesterol.

Statins have a profound effect on LDL cholesterol. Low doses decrease LDL cholesterol by about 25%, and large doses decrease levels by as much as 63% (Table 49-8). Reductions are significant within 2 weeks and maximal within 4 to 6 weeks. Because cholesterol synthesis normally increases during the night, statins are most effective when given in the evening. If statins are withdrawn, serum cholesterol will return to pretreatment levels. Hence, treatment must continue lifelong. The mechanism by which statins reduce cholesterol levels is discussed below.



Elevation of HDL Cholesterol.

Statins can increase levels of HDL cholesterol. Recall that low levels of HDL cholesterol (below 40 mg/dL) are an independent risk factor for CHD. Hence, by raising HDL cholesterol, statins can help reduce the risk of CV events. The objective is to raise levels to 50 mg/dL or more.

Nonlipid Beneficial Cardiovascular Actions.

There is increasing evidence that statins do more than just alter lipid levels. Specifically, they can promote plaque stability (by decreasing plaque cholesterol content), reduce inflammation at the plaque site, slow progression of coronary artery calcification, improve abnormal endothelial function, enhance the ability of blood vessels to dilate, reduce the risk of atrial fibrillation, and reduce the risk of thrombosis by (1) inhibiting platelet deposition and aggregation and (2) suppressing production of thrombin, a key enzyme in clot formation. All of these actions help reduce the risk of CV events.

Increased Bone Formation.

There is evidence that statins can promote bone formation, and may thereby reduce the risk of osteoporosis and related fractures. In animal studies, statins have increased bone formation, apparently by enhancing the activity of osteoblasts (the cells that lay down new bone). Several case-control studies in humans have shown an association between statin use and reduced risk of osteoporotic fractures. However, other case-control studies have failed to demonstrate a protective effect. The reason for this discrepancy could lie with the inherent weaknesses of case-control studies. Hence, the issue is likely to remain unresolved until data from randomized controlled trials are available. In the meantime, osteoporosis should be managed with bisphosphonates and other drugs of proven efficacy (see Chapter 73, Drugs Affecting Calcium Levels and Bone Mineralization).

Mechanism of Cholesterol Reduction

The mechanism by which statins decrease LDL cholesterol levels is complex, and depends ultimately on increasing the number of LDL receptors on hepatocytes (liver cells). The process begins with inhibition of hepatic HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. In response to decreased cholesterol production, hepatocytes synthesize more HMG-CoA reductase. As a result, cholesterol synthesis is largely restored to pretreatment levels. However, for reasons that are not fully understood, inhibition of cholesterol synthesis causes hepatocytes to synthesize more LDL receptors. As a result, hepatocytes are able to remove more LDLs from the blood. In patients who are genetically unable to synthesize LDL receptors, statins fail to reduce LDL levels, indicating that (1) inhibition of cholesterol synthesis, by itself, is not sufficient to explain cholesterol-lowering effects; and (2) in order for statins to be effective, synthesis of LDL receptors must increase.

In addition to inhibiting HMG-CoA reductase, statins decrease production of apolipoprotein B-100. As a result, hepatocytes decrease production of VLDLs. This lowers VLDL levels along with LDL levels. Statins also raise HDL levels by 5% to 22%.

Clinical Trials

Statins slow progression of CHD and decrease the risk of stroke, hospitalization, cardiac events, peripheral vascular disease, and death. Benefits are seen in men and women, and in apparently healthy people as well as those with a history of CV events. Hence, the statins are useful for both primary and secondary prevention. Furthermore, these drugs can even help people with normal LDL levels, in addition to those whose LDL is high. Statins can also protect people with diabetes.

Secondary Prevention Studies.

In patients with evidence of existing CHD (angina pectoris or previous MI), statins reduce the risk of death from cardiac causes. This was first demonstrated conclusively in the landmark Scandinavian Simvastatin Survival Study (4S). After 4.9 to 6.3 years of follow-up, the death rate was 12% among patients taking placebo and 8% among those taking simvastatin—a 30% decrease in overall mortality. Benefits were due to a decrease in cardiac-related mortality; deaths from noncardiac causes were the same in both groups.


The Cholesterol and Recurrent Events (CARE) trial demonstrated the ability of statins to reduce the risk of stroke in addition to coronary events. In this study, 4159 people with a history of MI were given pravastatin (40 mg daily) or placebo. After 5 years, the incidence of MI (fatal or nonfatal) was 13.2% in those taking placebo and 10.2% in those taking the drug. Pravastatin also produced a 26% decrease in the risk of stroke.

The Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) trial was the first to show that intensive reductions in LDL with statin therapy provide more CV protection than moderate reductions. In PROVE-IT, 4162 patients with acute coronary syndromes were randomized to either a moderate statin regimen (pravastatin, 40 mg daily) or an intensive statin regimen (atorvastatin, 80 mg daily). The result? LDL levels in the moderate group dropped to 95 mg/dL, compared with 62 mg/dL in the intensive group. Furthermore, not only did intensive therapy produce a greater decrease in LDL cholesterol, it produced a greater reduction in adverse outcomes: After 24 months, the incidence of CV events (death, MI, unstable angina, or revascularization) was only 22.4% in the intensive group compared with 26.3% in the moderate group. These results led the ATP III panel to recommend lower target LDL levels in patients at very high CV risk.

Primary Prevention Studies.

Two studies have demonstrated the ability of statins to reduce mortality in people with no previous history of coronary events. In the first trial—the West of Scotland Coronary Prevention Study (WOSCOPS)—6595 men with high cholesterol were given either pravastatin (40 mg/day) or placebo. During an average follow-up of 4.9 years, 4.1% of those taking placebo died, compared with only 3.2% of those taking the drug. The second trial—the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)—enrolled 6605 low-risk patients: men and women with average cholesterol levels (221 mg/dL) and no history of CV events. The subjects were randomly assigned to receive lovastatin (20 to 40 mg/day) or placebo. After an average follow-up of 5.5 years, the incidence of first major coronary events was 5.5% for those taking placebo and 3.5% for those taking the drug—representing a 36% decrease in risk.

Prevention in Patients with Normal Cholesterol Levels.

The landmark Heart Protection Study, published in 2002, was the first major trial to demonstrate that statins can reduce the risk of major coronary events in people who have normal levels of cholesterol. This double-blind, placebocontrolled trial enrolled 20,536 high-risk British patients: men and women with diabetes, prior MI, stroke, or angioplasty. Some had high levels of LDL and total cholesterol; others had normal levels. Subjects were randomly assigned to receive either simvastatin (40 mg/day) or placebo. After 5 years, the incidence of death was 12.9% in the treatment group, compared with 14.7% in the placebo group. Death from CHD was reduced by 18%. In addition, simvastatin reduced the risk of nonfatal MI by 38% and of stroke by 25%, and reduced the need for coronary revascularization (eg, angioplasty) by 30%. Most strikingly, benefits were seen in patients whose LDL cholesterol was normal or low, as well as in those whose levels were high. These data suggest a radical shift in practice. Specifically, they suggest we should treat people at high CHD risk—not simply those with high cholesterol levels. Obviously, doing so would greatly expand the number of patients receiving statin therapy.

Prevention in Patients with Diabetes.

Results of the Collaborative Atorvastatin Diabetes Study (CARDS) indicate that statin therapy can reduce the risk of CV events in diabetes patients, even if LDL levels are normal. This randomized trial, conducted in Britain and Ireland, enrolled 2838 patients with type 2 diabetes who had no history of CV disease. Half received 10 mg of atorvastatin [Lipitor] daily and half received a placebo. After a mean of 4 years, the combined incidence of acute coronary events, coronary revascularization, and stroke was only 5.8% in the atorvastatin group, compared with 9% in the placebo group, representing a 36% reduction in risk. These results suggest that statin therapy could benefit most patients with diabetes, regardless of their LDL level.

Therapeutic Uses

Indications for the statins keep expanding. When these drugs were introduced, they were approved only for hypercholesterolemia. As understanding of their benefits has grown, so has the list of indications. Today, statins have nine approved indications. The most recent additions are elevation of HDL cholesterol and prevention of CV events in people with type 2 diabetes. Indications for individual statins are summarized in Table 49-9. Major indications are discussed below.

Hypercholesterolemia.

Statins are the most effective drugs we have for lowering cholesterol. In sufficient dosage, statins can decrease LDL cholesterol by more than 60%. For many patients, the treatment goal is to drop LDL cholesterol to below 100 mg/dL. For patients at very high CV risk, a target of 70 mg/dL may be appropriate.

Primary and Secondary Prevention of CV Events.

As discussed, statins can reduce the risk of CV events (eg, MI, angina, stroke) in patients who have never had one (primary prevention) and they can reduce the risk of a subsequent event after one has occurred (secondary prevention). Risk reduction is related to the reduction in LDL: the greater the LDL reduction, the greater the reduction in risk.

Diabetes.

Cardiovascular disease is the primary cause of death in people with diabetes. Hence, to reduce mortality, controlling CV risk factors—especially hypertension and high cholesterol—is as important as controlling high blood glucose. The American Diabetes Association recommends a statin for all patients over the age of 40 whose total cholesterol is 135 mg/dL or higher—regardless of LDL cholesterol level. The American College of Physicians recommends a statin for (1) all patients with type 2 diabetes plus diagnosed CHD—even if they don't have high cholesterol; and (2) all adults with type 2 diabetes plus one additional risk factor (eg, hypertension, smoking, age over 55)—even if they don't have high cholesterol. Taken together, these guidelines suggest that most patients with diabetes should receive a statin.

Potential Uses.

Potential uses of statins extend well beyond diabetes and cardiovascular disorders. Judging from preliminary evidence, these drugs may eventually be used to prevent and/or treat a variety of conditions, including Alzheimer's disease, kidney disease, multiple sclerosis, macular degeneration, glaucoma, rheumatoid arthritis, weak bones, and even cancer.

Pharmacokinetics

Statins are administered orally. The amount absorbed ranges between 30% and 90%, depending on the drug. Regardless of how much is absorbed, most of an absorbed dose is extracted from the blood on its first pass through the liver, the principal site at which statins act. Only a small fraction of each dose reaches the general circulation. Statins undergo rapid hepatic metabolism followed by excretion primarily in the bile. Only three agents—lovastatin, pravastatin, and simvastatin—undergo clinically significant (10% to 20%) excretion in the urine.

Three statins—atorvastatin, lovastatin, and simvastatin—are metabolized by the 3A4 isozyme of cytochrome P450 (CYP3A4). As a result, levels of these drugs can be lowered by agents that induce CYP3A4 synthesis. More importantly, their levels can be increased—sometimes dramatically—by agents that inhibit CYP3A4 (see below).

One agent—rosuvastatin—reaches abnormally high levels in people of Asian heritage. At usual therapeutic doses, rosuvastatin levels in these people are twice those in whites. Accordingly, if rosuvastatin is used by Asians, dosage should be reduced.

Adverse Effects

Statins are generally well tolerated. Side effects are uncommon. Some patients develop headache, rash, or GI disturbances (dyspepsia, cramps, flatulence, constipation, abdominal pain). However, these effects are usually mild and transient. Serious adverse effects—hepatotoxicity and myopathy—are relatively rare. With one agent—rosuvastatin—serious effects may occur more often than with other statins.

Myopathy/Rhabdomyolysis.

Statins can injure muscle tissue. Mild injury, manifesting as muscle ache or weakness, occurs in 1% to 5% of patients. Rarely, muscle injury progress to myositis, defined as muscle inflammation associated with moderate elevation of creatine kinase (CK), an enzyme released from injured muscle. Myositis, in turn, may progress to potentially fatal rhabdomyolysis, defined as muscle disintegration or dissolution, associated with marked elevation of CK (greater than 10 times the upper limit of normal [ULN]) and possibly with renal failure. Fortunately, fatal rhabdomyolysis is extremely rare: the overall incidence is less than 0.15 cases per 1 million prescriptions. Patients should be informed about the risk of myopathy and instructed to notify the physician if unexplained muscle pain or tenderness occurs. How statins cause myopathy is unknown.

Several factors increase the risk of myopathy. Among these are advanced age, small body frame, frailty, multisystem disease (eg, chronic renal insufficiency, especially associated with diabetes), use of statins in high doses, concurrent use of fibrates or ezetimibe (which can cause myopathy themselves), and concurrent use of drugs that can raise statin levels (see below). In addition, hypothyroidism increases risk. Accordingly, if muscle pain develops, thyroid function should be assessed.

Measurement of CK levels can facilitate diagnosis. The level should be determined at baseline, and again if symptoms of myopathy appear. If the CK level is more than 10 times the ULN, the statin should be discontinued. If the level is less than 10 times the ULN, the statin can be continued, provided myopathy symptoms and the CK level are followed weekly. Routine monitoring of CK in asymptomatic patients is unnecessary.

Of the six statins in current use, rosuvastatin [Crestor] poses the highest risk of rhabdomyolysis. Among the other five, the risk is equally low. A seventh agent—cerivastatin [Baycol]—was withdrawn in 2001 because the risk was 16 to 80 times higher than with other statins.

Hepatotoxicity.

Liver injury, as evidenced by elevations in serum transaminase levels, develops in 0.5% to 2% of patients treated 1 year or longer. However, jaundice and other clinical signs are rare. Progression to outright liver failure occurs very rarely, if at all. Because of the risk of liver injury, product labeling recommends that liver function tests (LFTs) be done before treatment and every 6 to 12 months thereafter (see Table 49-8). However, there is evidence that routine monitoring may not really be needed. If serum transaminase levels rise to 3 times the ULN and remain there, statins should be discontinued. Transaminase levels decline to pretreatment levels following drug withdrawal.

Should statins be used by patients with active liver disease? The answer depends on the disease. In patients with viral or alcoholic hepatitis, statins should definitely be avoided. However, in patients with the most common cause of hepatitis—nonalcoholic fatty liver disease—statins are acceptable therapy. In fact, in these patients, not only can statins reduce cholesterol levels, they may also decrease liver inflammation, improve LFTs, and reduce steatosis (fatty infiltration in the liver). Should LFTs be monitored? Yes—at baseline and every 3 months thereafter. If LFTs climb to 3 times the ULN, statin use should stop.

Peripheral Neuropathy.

Very rarely, peripheral neuropathy develops in statin users. Symptoms include weakness, difficulty walking, and tingling and pain in the hands and feet. The underlying mechanism could be disruption of neuronal integrity secondary to inhibition of cholesterol synthesis. Statin-related neuropathy is often reversible, but may take 3 to 12 months to resolve. At this time, solid proof that statins cause neuropathy is lacking—although the available data are strongly suggestive. Hence, if symptoms of neuropathy develop, the statin should be suspected.

Drug Interactions

Fibrates and Ezetimibe.

Gemfibrozil, fenofibrate, and ezetimibe can cause myopathy, just like the statins. Accordingly, if these drugs are combined with a statin, the risk of myopathy is greater than with either agent alone. Clearly, the combination should be used with caution.

Agents That Inhibit CYP3A4.

Agents that inhibit CYP3A4 can raise levels of lovastatin and simvastatin substantially, and can raise levels of atorvastatin moderately. Important inhibitors of CYP3A4 include cyclosporine, macrolide antibiotics (eg, erythromycin), azole antifungal drugs (eg, ketoconazole), and HIV protease inhibitors (eg, ritonavir). If these drugs are combined with a statin, caution is advised. Some authorities recommend an automatic reduction in statin dosage. In addition to drugs, grapefruit juice can inhibit CYP3A4. However, to produce significant inhibition, the patient would have to drink about 1 quart a day.

Use in Pregnancy

Statins are classified in Food and Drug Administration Pregnancy Risk Category X: the risks to the fetus outweigh any potential benefits of treatment. When administered to pregnant rats in doses 500 times greater than the maximal recommended dosage for humans, lovastatin produced fetal skeletal malformations. Teratogenic effects in humans have not been reported. However, because statins inhibit synthesis of cholesterol, and since cholesterol is required for synthesis of cell membranes as well as several hormones, concern regarding human fetal injury remains. Moreover, there is no compelling reason to continue lipid-lowering drugs during pregnancy. Women of child-bearing age should be informed about the potential for fetal harm and warned against becoming pregnant. If pregnancy occurs, statins should be withdrawn.

Drug Selection

Several factors bear on statin selection, including LDL goal, drug interactions, kidney function, safety in Asians, and price.

LDL Goal.

If a 30% to 40% reduction in LDL is adequate, any statin will do. However, if LDL must be lowered by more than 40%, then atorvastatin or simvastatin is preferred. Although rosuvastatin is also highly effective, experience with this drug is limited, and hence we can't be as comfortable regarding its safety or ability to reduce CV events.

Drug Interactions.

Drugs that inhibit CYP3A4 can raise levels of atorvastatin, lovastatin, and simvastatin, thereby increasing the risk of toxicity, especially myopathy and liver injury. Accordingly, in patients taking a CYP3A4 inhibitor, other statins are preferred.

Kidney Function.

For patients with normal renal function, any statin is acceptable. However, for patients with significant renal impairment, atorvastatin or fluvastatin is preferred (because no dosage adjustment is needed).

Safety in Asians.

Rosuvastatin can reach abnormally high levels in Asians, and thus is a poor choice for these people.

Price.

One agent—lovastatin—is available as a generic product, and hence is cheaper than all other statins. For patients who need a modest reduction in LDL and are not taking a CYP3A4 inhibitor, lovastatin would be the best choice.

This is copied from my pharmacology textbook. The only thing I wished I could include here are the tables (they don't come out right). My opinion is that statins are mostly safe (meaning most people would not have any side effects). That being said just from the replies here you can tell some people had side effects even very serious ones. Statins are not for them. And some statins might work better for some people than others.
I was on statins a few years ago but stopped them when decided to have kids. My lipid profile i now is fine and I'm not taking them because I'm not quite done having kids and because I'm 26, have normal cholesterol levels (doesn't seem like I need them).

Hope I helped your understanding.
Mariya

[karen]

I wasn't aware of a blood test to see if statins were called for. There is a CACS scan (coronary artery calcium study) that can be done, though most insurance doesn't cover it. I'd get one of those before taking the debilitaing statin.

[Mariya Blas]

Yesterday, I went to see my endo and specifically asked him about starting Lipitor (or any statin, for that matter). He said the studies that showed the benefits of statins for diabetics were almost all for type 2's. He said I'm a little different. I explained my reluctance to just start taking a pill for taking a pill's sake - prophylactic effect.

He recommended that I have a relatively new blood test called h.s. CRP - high sensitivity c-reactive protein. He said if it came in low (<1), I probably didn't need the statin. If it was mid-range (1-3) it was pretty much a judgement call. If over 3, he would also recommend the statin.

I'll have the blood drawn in a couple of weeks before I go back to see the young heart doc. The jury's still out on her. I haven't decided whether to trust her like I do my endo.

I do want to thank everyone for their replies - y'all have really helped me a lot in making up my mind. I've had so many docs I didn't like/respect that I have to make up my mind what's best for me.

Tom

Here's some info about the CRP test. As you can see it's not very specific but it can be used to evaluate cardiovascular health. A high value, though could be caused by multiple diseases and should be interpreted in the context of other tests.


C-reactive protein test (CRP, High-sensitivity C-reactive protein [hs-CRP])

Type of test

Blood

Normal findings

<1.0 mg/dl or <10.0 mg/L (SI units)

Cardiac risk

Low <1.0 mg/dl

Average 1.0-3.0 mg/dl

High >3.0 mg/dl

Test explanation and related physiology

C-reactive protein is a nonspecific, acute-phase reactant used to diagnose bacterial infectious disease and inflammatory disorders such as acute rheumatic fever and rheumatoid arthritis. CRP levels do not consistently rise with viral infections. CRP is a protein produced primarily by the liver during an acute inflammatory process and other diseases. A positive test result indicates the presence but not the cause of the disease. The synthesis of CRP is initiated by antigen-immune complexes, bacteria, fungi, and trauma.

The CRP test is a more sensitive and rapidly responding indicator than the erythrocyte sedimentation rate (ESR). In an acute inflammatory change, CRP shows an earlier and more intense increase than ESR; with recovery, the disappearance of CRP precedes the return of ESR to normal. The CRP also disappears when the inflammatory process is suppressed by salicylates or steroids.

This test is also useful in evaluating patients with an acute myocardial infarction. The level of CRP correlates with peak levels of the MB isoenzyme of creatine kinase, but CRP peaks occur 1 to 3 days later. Failure of CRP to normalize may indicate ongoing damage to the heart tissue. Levels are not elevated in patients with angina.

Recent development of a high sensitivity assay for CRP (hs-CRP) has enabled accurate assays at even low levels. Atheromatous plaques in diseased arteries typically contain inflammatory cells. Multiple prospective studies also have demonstrated that baseline CRP is a good marker of future cardiovascular events. The C-reactive protein level is a stronger predictor of cardiovascular events than the low-density lipoprotein (LDL) cholesterol level. However, when used together with the lipid profile, it adds prognostic information to that conveyed by the Framingham risk score. Because of the individual variability in hs-CRP, two separate measurements are required to classify a person's risk level. In patients with stable coronary disease or acute coronary syndromes, hs-CRP measurement may be useful as an independent marker for assessing the likelihood of recurrent events, including death, myocardial infarction, or restenosis after percutaneous coronary intervention.